Pharmacokinetics of moxifloxacin in plasma and tissue of morbidly obese patients

Objectives: To assess the pharmacokinetics of moxifloxacin in morbidly obese patients. Methods: Twelve morbidly obese patients (2 male/10 female, age 25-61 years, weight 98-166 kg, body mass index 43.0-58.2 kg/m(2)) scheduled for gastric bypass surgery were treated with 400 mg of moxifloxacin orally once daily for 3 days and with 400 mg of moxifloxacin intravenously on day 4 (day of surgery). Pharmacokinetic analysis was performed on day 1 and day 4. Specimens of small intestine, greater omentum and subcutaneous adipose tissue were collected intraoperatively 1.8-3.7 h after moxifloxacin infusion. Moxifloxacin concentrations were determined by HPLC. Results: The plasma pharmacokinetics (mean +/- SD) was comparable to historical data in normal-weight subjects. Oral bioavailability was 79.6% +/- 11.5%. After intravenous administration, plasma clearance was 9.6 +/- 2.0 L/h, volume of distribution was 165 +/- 30 L and area under the curve was 43.7 +/- 11.8 mg.h/L. Linear regression analysis showed the volume of distribution to be better correlated with ideal body weight, lean body weight, fat-free mass or height (R(2) = 0.60-0.67, P = 0.001-0.003) than with total body weight (R(2) = 0.46, P = 0.015). Whereas mean tissue concentrations in small intestine (6.99 +/- 2.34 mg/kg) were twice the concomitant plasma concentrations, the concentrations in greater omentum (0.801 +/- 0.168 mg/kg) or subcutaneous fat (0.638 +/- 0.180 mg/kg) were only one-quarter of those. Conclusions: The pharmacokinetics of moxifloxacin is not significantly affected by morbid obesity. No dose adjustment seems to be necessary in this particular population.